Search

In an autopsy case of sporadic rapidly progressive lower motor neuron disease (MND), Gallyas-positive argyrophilic and ubiquitinated filamentous intracytoplasmic inclusions were found in the neurons. Clinically, 7 months prior to death, a 68-year-old woman experienced a history of rapidly progressive muscle weakness of all four extremities and bulbar sign, without sensory and autonomic disturbance. Two months later, she became unable to stand or walk. Four months after onset, she needed respiratory support, and subsequently died due to cardiorespiratory arrest. Neuropathological examinations revealed neuronal loss and associated gliosis in the lower motor neurons, except for ocular motor nuclei, Clark’s column, and accessory cuneate nucleus, and tract degeneration was observed in the middle root zone of the posterior column and spinocerebellar tract. No Bunina bodies or Lewy body-like hyaline inclusions were found in the anterior horns. Gallyas-positive argyrophilic filamentous inclusions were found in the lower motor neurons and in nerve cells of the Clark’s column, intermediate zone, posterior horn and accessory cuneate nucleus. These were positive with anti-ubiquitin antibody but negative with anti-tau (tau-2 and AT8) and neurofilament antibodies. Electron microscopic examinations disclosed randomly arranged tubular-like filamentous profiles, with a diameter of 12–14 nm, sometimes with amorphous granules in the perikaryon. This is the first report on the Gallyas-positive argyrophilic and ubiquitinated filamentous inclusions in neurons in MND.

A 65-year-old man with familial amyotrophic lateral sclerosis (ALS) with posterior column involvement showed fairly slow progression of the illness and lived with the aid of a respirator for 12 years. Neuropathological examinations showed simultaneous involvement of the pyramidal tract and lower motor neurons as well as degeneration in the Clarke’s nucleus- spinocerebellar tract- middle root zone of the posterior column, the pallido-luysian system, the medullary reticular formation, and widespread anterolateral columns of the spinal cord. However, the patient had no Lewy-body-like hyaline inclusions, which are characteristic features of this form of familial ALS. Moreover, no abnormalities were found in his SOD1 cDNA sequences. There seem to be certain heterogeneities in familial ALS with posterior column involvement, and SOD1 gene abnormalities may be involved in the pathomechanism in rapidly progressing ALS, in which there are Lewy-body-like hyaline inclusions.

We describe a new family with adult onset amyotrophic lateral sclerosis (FALS), in which the disease was characterized clinically by relatively rapid progression of bulbar symptoms. Gene analysis of Cu/Zn superoxide dismutase (SOD1) performed in one patient showed no mutations. Autopsy of another patient demonstrated degenerative changes restricted to the upper and lower motor neuron systems; no evident changes were observed in the posterior column, Clarke's column or spinocerebellar tracts. The presence of Bunina bodies and ubiquitin-positive skein-like inclusions in the lower motor neuron was of considerable interest. Cases of FALS with such pathological features are quite rare in the literature. Identification of the gene responsible for the disease is desirable in order to shed further light on the molecular pathology of not only familial, but also sporadic, ALS.

We report a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (FALS) with onset in the bulbar musculature, clinically benign course, absence of the Cu/Zn superoxide dismutase-1 (SOD 1) gene mutation, and many Bunina bodies, in addition to involvement of the upper and lower motor neurons. The proband was a Japanese woman who was 66 years old at the time of death. Family history disclosed five patients with FALS over three generations. She developed dysarthria at age 57, followed by dysphagia, muscle weakness of the upper extremities, and difficulty in respiration. She could walk without support until her death. The elder sister of the proband developed dysarthria at age 48 and died at age 58. A genetic study of the nephew of the proband showed the absence of a mutation in the SOD 1 gene. Neuropathological examination of the proband disclosed neuronal loss in the upper and lower motor neurons, and numerous Bunina bodies in the lower motor neurons without Lewy body-like inclusions or ubiquitin-immunoreactive neuronal inclusions. No degeneration of the Clarke's column, middle root zone of the posterior column, or posterior spinocerebellar tract was present. Review of the literature revealed that only patients with FALS with a long survival period of over 5 years had pathological findings consistent with FALS with posterior column involvement. This study contributes to the elucidation of the clinicopathological heterogeneity of FALS.

The present study was undertaken to obtain morphologic data about the posterior column of the spinal cord to characterize ascending myelinated axons of primary sensory neurons of the sciatic nerve. By applying doxorubicin to the right sciatic nerve in eight male Wistar rats, selective degeneration of centrally directed axons of these neurons in the posterior column was produced. Epon-embedded transverse sections of the posterior column at spinal cord segments C1, C3, C8, T6, L3 and L5 showed a circumscribed area (R) that contained a cluster of degenerated myelinated fibers. To characterize area R, its size and distances between various defined points on transverse sections of the posterior column were measured and compared at several spinal segments. The location of area R was illustrated in representative rats. The posterior intermediate septum corresponded to the lateral border of area R at C8 and T6. To characterize the putatively degenerating and degenerated myelinated fibers, area L in the left posterior column, corresponding to area R, was defined, and subsequently the number and size distribution of normal-appearing myelinated fibers in areas R and L were evaluated at C3, T6 and L3 in four rats. After comparative evaluation of these data, it was concluded that large myelinated fibers degenerated preferentially in area R. The number of putatively degenerating and degenerated myelinated fibers in area R at segments C3 and T6 was estimated to be 38.6% and 50.1%, respectively, of that at segment L3.

We report an autopsy case of respirator-assisted long-survival sporadic amyotrophic lateral sclerosis (ALS) with extensive involvement extending beyond the motor system. The involved areas included the globus pallidus, subthalamic nucleus, red nucleus, substantia nigra, Clarke's column, intermediolateral nucleus, Onuf's (Onufrowicz) nucleus, middle root zone of the posterior column, and the spinocerebellar tract. There was no impairment of ocular movements. Such sporadic ALS cases with extensive involvement extending beyond the motor system may constitute a distinct subgroup of this disease that differs from long-survival ALS (with or without respirator support) in which only the motor system is affected.

Axonal dystrophy in normal ageing can be studied in experimental animals. Primary sensory neurones show two different kinds of change with ageing, i.e. axonal dystrophy and axonal atrophy (degeneration). This paper reports the chronology and topography of these two processes in relation to growth and involution of these neurones throughout the lifespan of the rats used in this study. Axonal spheroids preferentially form at presynaptic terminal regions in many of the collaterals of central branches of the axons, i.e. in the posterior funiculus nuclei, posterior column and posterior funiculus. Axonal dystrophy in normal ageing is essentially a morbid process restricted to the terminal parts of the axon. It shows little tendency to expand retrogradely along the axon. Evidence is presented that spheroids in posterior funiculus also derive from terminal axons. Preference is also noted in the lumbosacral rather than cervical neurons, and in longer (posterior funiculus nuclei) rather than shorter (posterior column) collaterals. Quantitative study of myelinated fibres in posterior funiculus shows that they increase in number until middle age (400 days) of the animals, before beginning to decline. On the other hand, axonal atrophy begins to appear early in small numbers, and increases in numbers with age. Atrophy involves the whole length of the axon within the posterior funiculus from the start, suggesting, therefore, that it does not belong to a dying-back process. It is noteworthy that the main development of axonal dystrophy lies in the earlier half of the animals' life, while that of axonal atrophy lies in the latter half. This fact adds to the evidence that axonal dystrophy, as far as in normal ageing is concerned, is more related to the positive side of neuronal activity, e.g. one form of growth abnormality of axon.

This report describes pathologic findings of pencil-shaped softening in 12 autopsy cases. Nine cases were associated with extradural metastasis of malignant tumor and three were observed in brain death. The cavity of the pencil-shaped softening containing necrotic debris and abundant macrophages was located mainly in the ventral part of the posterior column or the dorsal horn. It extended longitudinally over several segments of the cord, predominantly in an upward direction, and had a very clear demarcated margin from the compressed surrounding tissue. Reactive change of the surrounding tissue was very rare. Pencil-shaped softening was found most often in the level of the thoracic cord. The cavity was always continuous with an area of transverse necrosis or and area of patchy necrosis. In previous reports, the factor of circulatory disturbance was considered important for the pathogenesis of pencil-shaped softening. In addition, we believe that mechanical compression is also an important factor.

An analysis is presented of the neuropathological findings in a 39-year-old man with severe multiple sclerosis who received two subarachnoid injections of phenol in glycerin for the relief of spastic paraparalysis in flexion contracture and of the findings in a single root from another patient. The morphology and extent of the pathological processes are described.

This report describes the pathologic findings in five autopsy cases with intramedullary spinal cord metastasis. In an autopsy series over a 30-year period, the incidence of intramedullary metastasis among the metastatic tumors to the spine was 3.5%, and the incidence among the central nervous system (CNS) metastasis was 4.2%. Primary site of tumor was the lung in four cases, and cancer of the thyroid was suspected in one case. On transverse section, the tumor was located mainly in the ventral part of the posterior horn and the medial part of the lateral column. Involvement was focal extending over one to six segments. In two cases, secondary hemorrhage occurred in the posterior horn or the posterior column. In three cases, central ischemic infarction was noted cephalad and caudad to the tumor metastasis. The mode of tumor spread to the spinal cord is not clear, but the autopsy findings in our series suggest that intramedullary tumor may result from hematogenous spread via the arterial circulation.